The following information is provided to assist the reader in understanding technologies disclosed below and the environment in which such technologies may typically be used. The terms used herein are not intended to be limited to any particular narrow interpretation unless clearly stated otherwise in this document. References set forth herein may facilitate understanding of the technologies or the background thereof. The disclosure of all references cited herein are incorporated by reference.
CO2 is an end-product of energy metabolism in all mammals, including humans. Under normal circumstances, it is removed by expiration. CO2 is transported to the lungs by the blood stream, where it exists mostly in the form of bicarbonate (HCO3−) as a result of the following equilibrium reaction:CO2+H2O<=>H2CO3<=>H++HCO3−  (1)
High levels of CO2 may be tolerated to some extent, but, if not corrected, lead to progressive mental obtundation, reduced respiratory drive, and resultant alveolar hypoventilation, hypoxemia, acidosis and death. Many critically ill patients, therefore, require mechanical ventilation in the intensive care unit. Mechanical ventilation, although indispensable for survival, may worsen the injured lung and may increase the mortality rate if inappropriately administered. This is particularly true for acute respiratory distress syndrome (ARDS), in which several studies demonstrated that the main reason for high mortality (30-50%) is not severe hypoxemia but rather multi-organ failure (kidneys, heart, liver, etc.), potentially caused by the translocation of various mediators from the lungs through the systemic circulation to peripheral organs and/or augmented by artificial ventilation (ventilator-induced lung injury, VILI). There is good evidence that low volume lung protective ventilation (LPV) improves outcomes in ARDS, but there is also evidence that hypercapnia (high plasma CO2 levels) as a result of reduction of ventilatory volumes prevents the successful application of LPV. Furthermore, recent studies have shown that lung hyperinflation still occurs in approximately 30% of ARDS patients, even though they are being ventilated “correctly” using the National Heart, Lung, and Blood Institute ARDS Network (ADRSNet) strategy. These studies also suggested that some patients may benefit from a further reduction of tidal volume (VT) even when peak plateau pressure (PPLAT) is less than 30 cm H2O.
Extracorporeal carbon dioxide removal (ECCOR) is a technology that has been available for 40 years, and has helped in addressing this problem to an extent. ECCOR involves removal of blood from the patient, which is pumped through an artificial lung (oxygenator membrane) where CO2 is removed and subsequently the purified blood is returned to the patient. However, ECCOR through an artificial lung is under-utilized, largely because it is only available in specialist centers and is complicated to use.
Continuous Renal Replacement Therapy (CRRT), is a widely available and less invasive technology than ECCR. Normally, CRRT (like routine hemodialysis) adds bicarbonate (or buffers such as acetate that are metabolized to bicarbonate) to the blood. Attempts to remove CO2/bicarbonate using CRRT have failed because of the development of metabolic acidosis despite addition of a base (typically, in the form of sodium hydroxide) to the returning blood. Attempts to replace bicarbonate with another anion such as tris(hydroxymethyl)aminomethane (TRIS), acetate, citrate and lactate also failed.